MPEP, a selective non-competitive antagonist of group I metabotropic glutamate receptor subtype 5 (mGluR5), administered at doses ranging from 0.75 to 1 mg/kg, failed to influence the electroconvulsive threshold in mice. However, when administered at higher doses (1.25 and 1.5 mg/kg), it significantly increased the threshold. Moreover, MPEP (applied at its highest subprotective dose of 1 mg/kg) did not affect the protective action of valproate, carbamazepine, diphenylhydantoin and phenobarbital against maximal electroshock-induced seizures in mice. The presented results indicate that mGluR5 antagonists should not be considered as good candidates for add-on therapy of generalized seizures.
In each experiment, one group of mice received spared nerve injury (SNI) surgery to model chronic pain; the other group received a control sham surgery. Both fenobam and MPEP induced preference in the SNI mice, such that SNI mice spent significantly more time in the mGluR5 antagonist-paired chamber compared to a vehicle-paired chamber. No such preference developed for sham mice. Morphine induced preference in male and female mice in both the SNI and sham groups.Glutamate, the major excitatory neurotransmitter in the brain, acts on both ionotropic and metabotropic glutamate receptors. Excessive metabotropic glutamate receptor (mGluR) transmission has been linked to epilepsy, ischemia, pain, anxiety, and depression. Eight subtypes (1-